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Vitamins
Vitamins, taken in the proper amounts, are essential for health
maintenance the prevention of certain diseases such as scurvy, rickets,
pellagra. They are generally considered healthy harmless, even in doses
far exceeding the recommended daily allowance (RDA) are touted to
enhance athletic performance prevent the common cold, facilitate weight
loss, treat a multitude of medical ailments. However, taken in excess
either chronically or acutely, many vitamins can cause significant
toxicity. The fat-soluble vitamins A and D accumulate in the body’s fat
stores when taken in excessive doses over time. Chronic vitamin A and D
toxicity has been widely reported.The water-soluble vitamins (the vitamin
B complex and ascorbic acid) are commonly thought to be safe because
they are readily excreted in the urine. However, these vitamins also
produce toxicity when taken in excessive amounts.
VITAMIN A
The RDA is 5000 IU for adults and 2000 to 3000 IU for children.
Action OF V.A:.It regulates the synthesis of proteins, bone metabolism,
and the processes of cell differentiation and keratinization in epithelial
tissues such as the skin, hair, and nails.
Hypervitaminosis A
Pathophysiology
Retinol mobilized from the liver is transported bound to retinol-binding
protein (RBP).Toxicity results when the carrying capacity of the RBPs is
overwhelmed and free retinol is available to bind with cellular
lipoproteins.Vitamin A lyses cell membranes and inhibits membraneassociated processes in animal models.The toxic effects of retinol at these
target tissues produce the characteristic dermatologic abnormalities of
hypervitaminosis A, as well as bone and cartilage resorption, cortical
hyperostosis, and periosteal calcifications.In the liver, storage of excess
vitamin A causes hyperplasia and hypertrophy of the perisinusoidal
stellate cells, perisinusoidal fibrosis, and cirrhosis that presents clinically
as hepatosplenomegaly, portal hypertension, mild to moderate
transaminase elevations, and, rarely, death. The mechanism by which
hypervitaminosis A produces pseudotumor cerebri is not known.
Clinical Presentation
The diagnosis of vitamin A toxicity, especially in the chronic form, is
often delayed because of the relatively nonspecific nature of the
symptoms and effects on multiple organ systems.
• History of excessive intake of preformed vitamin A
• Chronic hypervitaminosis A: brittle nails, dry scaling skin, alopecia,
arthralgias, hepatosplenomegaly, ascites, headache, bone pain,
hypercalcemia
• Acute hypervitaminosis A: headache, lethargy and/or irritability,
nausea, vomiting, delayed generalized desquamating rash
• Evidence of elevated intracranial pressure (pseudotumor cerebri)
including headache, papilledema, bulging fontanelles in children, nausea,
vomiting, blurred vision, and/or diplopia.
Treatment
1- Most signs and symptoms resolve spontaneously after the withdrawal
of all sources of vitamin A. Brittle nails, coarse hair, and alopecia may
persist for weeks after discontinuation of vitamin A supplementation but
should resolve.
2-Treatment of hypercalcemia includes intravenous fluid hydration and
monitoring of renal function.
3-Furosemide may increase renal calcium excretion.
4-Prednisone in an adult in a dose of 20 mg/d orally has also been used
to treat vitamin A–induced hypercalcemia.
5-Pseudotumor cerebri can be treated with lumbar punctures to remove
cerebrospinal fluid and with diuretics and prednisone
VITAMIN D
The RDA of vitamin D for adults and children is 400 IU.
Pharmacology
Vitamin D is well absorbed from the gut and stored in fat deposits. It is
also synthesized in the skin. It functions as a hormone to regulate calcium
homeostasis by increasing gut absorption of calcium and decreasing
calcium excretion by the kidneys
Hypervitaminosis D
Pathophysiology
Hypervitaminosis D can result from excessive vitamin D dietary
supplementation,inaccurately and excessively fortified dairy products,
prolonged use of vitamin D–fortified infant formulas,or ingestion of
vitamin D rodenticides. Iatrogenic hypervitaminosis D is seen in poorly
monitored vitamin D therapy for disorders such as rickets and
hypoparathyroidism. The toxic manifestations are due to hypercalcemia.
Clinical Presentation
• History of excessive intake of vitamin D2 (calciferol) or D3
(cholecalciferol)
•Signs and symptoms of hypercalcemia, including weakness, headache,
polyuria, polydipsia, anorexia, nausea, vomiting, altered mental status,
weight loss or failure to thrive, bone and/or abdominal pain, and cardiac
dysrhythmias
•Other findings of hypercalcemia, normal or elevated phosphorus levels,
albuminuria, hypercalciuria, ectopic soft tissue calcifications, and
pancreatitis
Treatment
1- Initial management is the withdrawal of all exogenous sources of
vitamin D and a low-calcium, low-vitamin D diet.
2- Treatment of hypercalcemia includes intravenous fluid hydration
and monitoring of renal function. Furosemide may increase renal
calcium excretion. Glucocorticoids have been effective in
reducing serum calcium levels, although the primary mechanism
is unclear.
VITAMIN C
Vitamin C is an essential dietary nutrient because it cannot be
synthesized by humans. The RDA for vitamin C is 60 mg for adults and
40 mg for children.
Pharmacology
Vitamin C (ascorbic acid) is a required cofactor for the function of a
number of enzymes involved in hydroxylation and amidation reactions,
such as collagen and proteoglycan synthesis, and microsomal drug
metabolism. It is readily absorbed from GIT by a saturable, energydependent process. At lower concentrations, metabolism in the liver
produces a number of metabolites, including oxalate. At higher
concentrations, unchanged vitamin C is also excreted in the urine.
Pathophysiology : Insufficient dietary intake of vitamin C causes
scurvy.Excessive vitamin C intake has been found to increase the urinary
excretion of oxalate.Several cases of severe hemolysis have been reported
after high doses of oral and intravenous vitamin C.The mechanism by
which vitamin C induces hemolysis is unknown. However, patients with
glucose-6-phosphate dehydrogenase (G6PD) deficiency or paroxysmal
nocturnal hemoglobinuria may be at higher risk.
Clinical Presentation
Patients with significant vitamin C toxicity are uncommon and are
usually receiving doses as high as 40 to 80 g/day (orally and/or
intravenously) as part of megadose vitamin therapies. Indications range
from cancer and schizophrenia to acquired immunodeficiency syndrome
(AIDS). Excessive vitamin C intake most commonly causes
gastrointestinal symptoms, including nausea, abdominal cramping, and
diarrhea. Large acute oral ingestions or large intravenous doses of
vitamin C have caused hemolysis, with resultant anemia and
hemoglobinuria.Patients with pre-existing hemoglobinopathies or
enzymopathies may be at higher risk for hemolysis.
Treatment
All sources of vitamin C should be withdrawn, and supportive therapies
including antiemetics should be administered as needed. Significant
vitamin C–induced hemolysis requires intravenous hydration to maintain
adequate urine output, monitoring of renal function, and transfusions as
needed for anemia .
VITAMIN B6(pyridoxine)
The RDA is 2.0 mg for adults and 0.5 to 1.0 mg for children.
Pharmacology
Pyridoxal phosphate functions as a coenzyme in decarboxylation,
transamination reactions in amino acid metabolism. Pyridoxine is
required for the conversion of tryptophan to 5-hydroxytryptamine
(serotonin), as well as dopa to dopamine. Pyridoxine is also essential for
the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid
(GABA) by the enzyme glutamate decarboxylase. It is well absorbed
from the gastrointestinal tract, and pyridoxal phosphate is the primary
circulating form. It undergoes hepatic metabolism to 4-pyridoxic acid.
Pathophysiology
Pyridoxine deficiency causes decreased brain GABA levels, thought to
be the cause of seizures seen in patients with pyridoxine deficiency ]
Isoniazid (INH) antagonizes the action of pyridoxine at several sites,
causing a clinical picture similar to that of pyridoxine deficiency.
In excess amounts, taken either acutely or chronically, pyridoxine
produces a pure sensory neuropathy.
Clinical Presentation
The predominant feature seen in both acute and chronic pyridoxine
toxicity is a sensory neuropathy. The patient may complain of difficulty
walking, loss of balance, and loss of manual dexterity. Signs include:
decreased touch, proprioception, temperature, and vibration. Reflexes are
absent, and motor strength is preserved. Patients may be ataxic or have a
wide-based gait. Symptoms may persist or progress for 2 to 3 weeks after
pyridoxine is discontinued.
Treatment
All sources of supplemental pyridoxine should be withdrawn.
NIACIN( vitamin B3)
• The RDA for niacin is 20 mg for adults and 9.0 mg for children.
• Niacin toxicity may present as an acute vasodilatory syndrome or as a
subacute hepatotoxic syndrome. Niacin-induced vasodilatory symptoms
are thought to be prostaglandin-mediated and are lessened by taking an
aspirin daily while on niacin therapy.The mechanism of niacin-induced
hepatotoxicity is unknown.
• Ingestion of immediate-release (IR), or crystalline, niacin produces
flushing, nausea, headache, vasodilation, and pruritus.
• Sustained-release (SR) preparations of niacin have a lower incidence of
these symptoms but a higher incidence of gastrointestinal complaints and
hepatotoxicity.
• Signs and symptoms of niacin toxicity should resolve after its use is
discontinued.